The present invention relates to magnetic nanoparticles and related devices and methods. More specifically, the present invention relates to compositions and methods of making magnetic nanoparticles having a narrow size distribution for use in diagnostics and therapeutics.
Magnetic nanoparticles (also referred to as MNPs) are attractive agents for biomedicine due to strong intrinsic magnetism that, through interaction with a magnetic field, enables their detection or influence from deep within a living subject. Rightly, magnetic nanoparticles have been studied extensively as potential contrast agents or nanoparticle materials in molecular imaging applications based on magnetic resonance imaging (MRI), as well as carriers for magnetically assisted drug delivery and hyperthermia. Recently, a new imaging modality called magnetic particle imaging (MPI) was introduced as a technique for visualizing magnetic nanoparticles in humans and animals. MPI is fast, quantitative, sensitive, and features good spatial resolution, a combination that is difficult to realize in MR imaging of magnetic nanoparticles, because MPI directly probes the large magnetic nanoparticle moment rather than its indirect effect on proton relaxation, as does MR imaging. Noteworthy recent MPI studies include in vivo, real-time imaging of magnetic nanoparticles passing through a beating mouse heart and compact, single-sided scanners that can image a patient without first inserting them into a costly and potentially claustrophobic magnetic device.
Despite much exciting progress in MPI scanner design and related image processing, relatively little effort has been spent developing magnetic nanoparticles that optimize imaging sensitivity. In fact, for MPI to successfully move beyond proof-of-principle experiments into the clinic or preclinical research laboratory, it will be important to engineer magnetic nanoparticles that are optimized for MPI. Most recent studies have used commercially available magnetic nanoparticle agents, including Resovist® (Bayer Schering Pharma, Berlin) and Feridex I.V.® (AMAG Pharmaceuticals, Lexington, Mass.; trade name Endorem™ in Europe); these are far from being magnetically optimized for MPI and thus inhibit MPI from reaching its full potential in terms of both spatial resolution and mass sensitivity. For example, in Resovist®, which to date has been the most popular material for MPI studies, it has been shown that only 3% of the total sample mass contributes noticeably to the MPI signal. More efficient nanoparticles are desired for molecular imaging applications that depend on active targeting, where for the highest sensitivity, each unit of nanoparticle is desired to generate the maximum achievable MPI signal voltage. Furthermore, for quantitative imaging, the signal intensity, and therefore magnetic nanoparticle properties, are desired to be uniform and reproducible.
In addition, magnetic nanoparticles are an attractive option for site-specific cancer therapies because they can be remotely targeted by the application of external magnetic field gradients or other active and passive targeting methods. Once localized, Magnetic Fluid Hyperthermia (MFH), a therapeutic modality that utilizes alternating magnetic fields (AMF) to dissipate heat from the resulting relaxation losses in magnetic nanoparticles, can be used to induce localized heating. Heating cancer cells (typically to ˜42-43° C.) is known to disrupt cellular metabolism making adjuvant therapy by conventional established methods more efficient. A wide range of ferromagnetic nanoparticles can be synthesized for MFH. Due to their modest magnetic characteristics, however, magnetic nanoparticles need to be optimized in terms of their morphological (size, size distribution, shape), crystallographic (phase purity) and magnetic (relaxation) characteristics for effective application in MFH.
Unfortunately, current methods of making magnetic nanoparticles do not provide ample control over morphological (size, size distribution, shape), crystallographic (phase purity) and magnetic (relaxation) characteristics that can improve existing diagnostic and/or therapeutic techniques using magnetic nanoparticles. Thus, a need exists for improved magnetic nanoparticles suitable for use in various diagnostic and/or therapeutic techniques.